Direct immunofluorescence (DIF) is the go-to diagnostic test when evaluating vesiculobullous eruptions, connective tissue disease, and vasculitis. This specialized test allows visualization of autoantibodies and their reaction products in the epidermis and dermis (skin) and epithelium and subepithelium (mucosa). Indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) are additional tests that can help in the diagnosis of autoimmune blistering disease. In the blistering autoimmune diseases, the autoantibodies target components in skin and mucous membranes that are essential for cell-cell and cell-matrix adhesion causing separation within or beneath the epidermis, depending on where the target components are located. This article is intended to serve as a helpful primer for immunofluorescence testing in dermatology, with an overview of the tests available as well as pragmatic tips for optimal biopsy sites and specimen transport.

Direct Immunofluorescence

Immunofluorescence techniques date back to 1941 when Albert Coons, an American physician, pathologist, and immunologist, fluorescently labelled antibodies to visualize pneumococcal antigens in infected tissues.^1-3 In dermatology, similar methodology was used to visualize the deposition of immunoglobulins and complement in the skin of patients with systemic lupus erythematosus in 1963.⁴ Basement membrane zone antibodies were first visualized via DIF in bullous pemphigoid in 1967.⁵ This elegant test utilizes specific antibodies labeled with fluorophores that are then incubated with the patient’s tissue, ultimately forming antibody-antigen conjugates that can be visualized with a fluorescent microscope. Antibodies usually include IgG, IgM, IgA, fibrinogen, and C3. Some institutions also evaluate for IgG4.

Transport medium is critical for proper evaluation of tissues using DIF. Inappropriate storage of tissue can degrade the antigen and confuse the interpretation of specimens. An acceptable medium for DIF includes Michel transport medium, which allows tissue to be stored for days while being transported at ambient temperature without loss of signal.^6,7 Zeus medium also can be used and is more readily available. Alternatively, biopsy tissue can be snap frozen using liquid nitrogen. Specimens also may be stored on saline gauze but should be analyzed within 24 to 48 hours.⁸ Most importantly, do not place the specimen in formalin; even a brief soak in formalin can greatly alter results, especially when trying to diagnose pemphigus.⁹ Proper transport conditions are critical to prevent autolysis, mitigate putrefaction, and preserve morphology while maintaining antigenicity.¹⁰

Indirect Immunofluorescence

Indirect immunofluorescence can be helpful for detecting antibodies circulating in patient serum. Indirect immunofluorescence can be used to help diagnose pemphigoid, pemphigus, epidermolysis bullosa acquisita, bullous lupus erythematosus, and dermatitis herpetiformis. Serum testing also can be a helpful alternative when obtaining tissue is difficult, such as in children.

Indirect immunofluorescence is a 2-part technique that takes a bit longer to assay than DIF.¹¹ The first step involves incubating prepared tissue substrates with patient serum. Unlabeled antibodies in the patient serum are allowed to bind to antigens in the substrate tissue for about 30 minutes. Doubling dilutions of patient serum can be performed to titer antibody levels. The second step uses fluorescein-labeled antihuman antibodies to recognize the antigen-antibody conjugates. Normal whole tissues (eg, monkey esophagus for pemphigus vulgaris, rat bladder for paraneoplastic pemphigus, salt-split normal human skin substrate for pemphigoid and epidermolysis bullosa) are the usual substrates for testing.^11,12 Again, this test requires serum and should be collected in a red-top tube or serum-separator tube. Usually, a minimum of 0.5 mL is required for testing, but check with your preferred immunodermatology send-out laboratory before collecting.¹³

Indirect immunofluorescence usually involves an initial screening panel using 1 or 2 tissue substrates followed by individual antigen-specific assays that correspond to the clinical suspicion and IIF screening results.¹¹ Salt-split skin is used to localize basement membrane zone autoantibodies to either the epidermal (roof) or dermal (floor) side. Although many dermatopathology laboratories offer DIF testing, IIF is more specialized and may be a send-out test at your institution.

Enzyme-linked Immunosorbent Assays

Another tool in the immunodermatology armamentarium is ELISA. Commercial ELISA systems are available for the detection of autoantibodies against bullous pemphigoid (BP) antigen 180, BP230, type VII collagen, desmoglein (Dsg) 1, Dsg3, and envoplakin.¹¹ This test allows semiquantitative measurement of antibody levels and thus can be used to monitor response to treatment or identify relapse and treatment failure.¹¹ For example, in BP, significantly increased baseline anti-BP180 IgG levels correlate with 1-year mortality rates (P=.001) and relapse rates (P=.041).^14,15 Numerous additional studies support the observation that monitoring anti-BP180 as a potential marker of disease relapse can be helpful.^16,17 In pemphigus, the presence or increase of autoantibodies at remission, either anti-Dsg3 or anti-Dsg1, may be a useful tool in predicting disease relapse.¹⁸ It is important for physicians to be aware of this to be able to offer guidance on prognosis.

Knowing where to biopsy can be confusing when beginning residency. But the short answer is, it depends. Let your clinical suspicion guide your specimen site. The Figure provides a quick reference for which location will give you the highest yield for a specific diagnosis.

A few cardinal rules should guide which site is biopsied. Avoid obtaining specimens from the lower extremities as much as possible, as this site has been linked with false-negative results, especially in bullous pemphigoid.^19,20 As a dependent area prone to stasis, this site gets a lot of abuse and inflammatory changes secondary to everyday insults that can theoretically alter DIF findings, especially fibrinogen deposition.

Although tissue sent for hematoxylin and eosin staining should be lesional, biopsy for DIF ideally should not contain a new or active blister, ulcer, erosion, or bulla. Immunoreactants are more likely to be degraded in these areas, and DIF may be falsely negative.²¹

It is worthwhile to briefly discuss the definitions of the terms perilesional and nonlesional. Perilesional skin most frequently refers to skin adjacent to a bulla or vesicle. This skin can be erythematous/inflamed or appear normal. When obtaining tissue for a diagnosis of blistering disease, the general recommendation is to obtain the biopsy from lesional nonbullous skin or perilesional uninvolved skin within 1 cm of the bulla.^22-24 The only exception to this is dermatitis herpetiformis, which is best diagnosed on tissue obtained from normal-appearing perilesional skin within 1 cm of an active lesion.²⁵ Additionally, if your patient has oral disease, the recommendation is to obtain the biopsy from nonlesional buccal mucosa, especially if there is desquamative gingivitis.^26,27

The ideal biopsy size is 4 or 5 mm. If considering both DIF and histopathology, it is best to procure 2 separate specimens. One larger biopsy can be carefully bisected in 2 but often is subject to more handling artifacts, which can affect findings. In the case of 1 biopsy bisected into 2 specimens, the punch should be at least 6 mm. Shave biopsies also can be performed as long as they extend into the reticular dermis.²³

For vasculitis, biopsies for DIF should be taken from lesions that are less than 24 hours old for highest yield, as the level of tissue immunoreactants tends to decline over time.²⁸ This guideline does differ from hematoxylin and eosin specimens sent for evaluation of vasculitis, which ideally should be lesional tissue over 72 hours old. When evaluating for lupus (including subacute cutaneous lupus, discoid lupus, and systemic lupus), DIF is more likely to be positive in well-established, active lesions.

Which Test Should I Order?

The answer to this question depends, but the use of all 3 tests has a specificity close to 100% when evaluating for autoantibody-associated diseases.²³ For autoimmune blistering disease, DIF is considered the diagnostic standard. The sensitivity of DIF for diagnosing BP is in the range of 82% to 90.5%, while specificity is 98%.^29-31 Other autoimmune blistering diseases, such as pemphigus or dermatitis herpetiformis, have even higher sensitivities and specificities. Direct immunofluorescence often is used as a screening test, but false negatives do occur.^32,33 Although rare, false positives also can occur, especially in cases of infection, and should be suspected when there is a lack of clinicopathologic correlation.³⁴ If DIF is negative but clinical suspicion remains high, IIF should be ordered to directly evaluate a patient’s serum for autoantibodies.

In acute cutaneous lupus, subacute cutaneous lupus, and discoid lupus, DIF of active lesions may be helpful if histopathologic examination of a cutaneous lupus erythematosus lesion is nondiagnostic. However, histopathologic examination of formalin-fixed tissue remains the standard for these diagnoses. In vasculitis, while DIF is not used for diagnosis, it is useful to evaluate for IgA deposition. This is important in adults, as IgA deposition has been associated with a greater risk for developing end-stage renal disease.³⁵

Final Thoughts

This is an overview of the tests available for diagnosing autoimmune blistering diseases. Residents should keep in mind that these tests are just one part of the puzzle when it comes to diagnosing these diseases. Results of DIF, IIF, and ELISA testing should be considered in conjunction with patient history and physical examination as well as histopathologic examination of lesional tissue when evaluating for dermatologic diseases with autoantibodies.

Direct immunofluorescence (DIF) is the go-to diagnostic test when evaluating vesiculobullous eruptions, connective tissue disease, and vasculitis. This specialized test allows visualization of autoantibodies and their reaction products in the epidermis and dermis (skin) and epithelium and subepithelium (mucosa). Indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) are additional tests that can help in the diagnosis of autoimmune blistering disease. In the blistering autoimmune diseases, the autoantibodies target components in skin and mucous membranes that are essential for cell-cell and cell-matrix adhesion causing separation within or beneath the epidermis, depending on where the target components are located. This article is intended to serve as a helpful primer for immunofluorescence testing in dermatology, with an overview of the tests available as well as pragmatic tips for optimal biopsy sites and specimen transport.

Direct Immunofluorescence

Immunofluorescence techniques date back to 1941 when Albert Coons, an American physician, pathologist, and immunologist, fluorescently labelled antibodies to visualize pneumococcal antigens in infected tissues.^1-3 In dermatology, similar methodology was used to visualize the deposition of immunoglobulins and complement in the skin of patients with systemic lupus erythematosus in 1963.⁴ Basement membrane zone antibodies were first visualized via DIF in bullous pemphigoid in 1967.⁵ This elegant test utilizes specific antibodies labeled with fluorophores that are then incubated with the patient’s tissue, ultimately forming antibody-antigen conjugates that can be visualized with a fluorescent microscope. Antibodies usually include IgG, IgM, IgA, fibrinogen, and C3. Some institutions also evaluate for IgG4.

Transport medium is critical for proper evaluation of tissues using DIF. Inappropriate storage of tissue can degrade the antigen and confuse the interpretation of specimens. An acceptable medium for DIF includes Michel transport medium, which allows tissue to be stored for days while being transported at ambient temperature without loss of signal.^6,7 Zeus medium also can be used and is more readily available. Alternatively, biopsy tissue can be snap frozen using liquid nitrogen. Specimens also may be stored on saline gauze but should be analyzed within 24 to 48 hours.⁸ Most importantly, do not place the specimen in formalin; even a brief soak in formalin can greatly alter results, especially when trying to diagnose pemphigus.⁹ Proper transport conditions are critical to prevent autolysis, mitigate putrefaction, and preserve morphology while maintaining antigenicity.¹⁰

Indirect Immunofluorescence

Indirect immunofluorescence can be helpful for detecting antibodies circulating in patient serum. Indirect immunofluorescence can be used to help diagnose pemphigoid, pemphigus, epidermolysis bullosa acquisita, bullous lupus erythematosus, and dermatitis herpetiformis. Serum testing also can be a helpful alternative when obtaining tissue is difficult, such as in children.

Indirect immunofluorescence is a 2-part technique that takes a bit longer to assay than DIF.¹¹ The first step involves incubating prepared tissue substrates with patient serum. Unlabeled antibodies in the patient serum are allowed to bind to antigens in the substrate tissue for about 30 minutes. Doubling dilutions of patient serum can be performed to titer antibody levels. The second step uses fluorescein-labeled antihuman antibodies to recognize the antigen-antibody conjugates. Normal whole tissues (eg, monkey esophagus for pemphigus vulgaris, rat bladder for paraneoplastic pemphigus, salt-split normal human skin substrate for pemphigoid and epidermolysis bullosa) are the usual substrates for testing.^11,12 Again, this test requires serum and should be collected in a red-top tube or serum-separator tube. Usually, a minimum of 0.5 mL is required for testing, but check with your preferred immunodermatology send-out laboratory before collecting.¹³

Indirect immunofluorescence usually involves an initial screening panel using 1 or 2 tissue substrates followed by individual antigen-specific assays that correspond to the clinical suspicion and IIF screening results.¹¹ Salt-split skin is used to localize basement membrane zone autoantibodies to either the epidermal (roof) or dermal (floor) side. Although many dermatopathology laboratories offer DIF testing, IIF is more specialized and may be a send-out test at your institution.

Enzyme-linked Immunosorbent Assays

Another tool in the immunodermatology armamentarium is ELISA. Commercial ELISA systems are available for the detection of autoantibodies against bullous pemphigoid (BP) antigen 180, BP230, type VII collagen, desmoglein (Dsg) 1, Dsg3, and envoplakin.¹¹ This test allows semiquantitative measurement of antibody levels and thus can be used to monitor response to treatment or identify relapse and treatment failure.¹¹ For example, in BP, significantly increased baseline anti-BP180 IgG levels correlate with 1-year mortality rates (P=.001) and relapse rates (P=.041).^14,15 Numerous additional studies support the observation that monitoring anti-BP180 as a potential marker of disease relapse can be helpful.^16,17 In pemphigus, the presence or increase of autoantibodies at remission, either anti-Dsg3 or anti-Dsg1, may be a useful tool in predicting disease relapse.¹⁸ It is important for physicians to be aware of this to be able to offer guidance on prognosis.

Knowing where to biopsy can be confusing when beginning residency. But the short answer is, it depends. Let your clinical suspicion guide your specimen site. The Figure provides a quick reference for which location will give you the highest yield for a specific diagnosis.

A few cardinal rules should guide which site is biopsied. Avoid obtaining specimens from the lower extremities as much as possible, as this site has been linked with false-negative results, especially in bullous pemphigoid.^19,20 As a dependent area prone to stasis, this site gets a lot of abuse and inflammatory changes secondary to everyday insults that can theoretically alter DIF findings, especially fibrinogen deposition.

Although tissue sent for hematoxylin and eosin staining should be lesional, biopsy for DIF ideally should not contain a new or active blister, ulcer, erosion, or bulla. Immunoreactants are more likely to be degraded in these areas, and DIF may be falsely negative.²¹

It is worthwhile to briefly discuss the definitions of the terms perilesional and nonlesional. Perilesional skin most frequently refers to skin adjacent to a bulla or vesicle. This skin can be erythematous/inflamed or appear normal. When obtaining tissue for a diagnosis of blistering disease, the general recommendation is to obtain the biopsy from lesional nonbullous skin or perilesional uninvolved skin within 1 cm of the bulla.^22-24 The only exception to this is dermatitis herpetiformis, which is best diagnosed on tissue obtained from normal-appearing perilesional skin within 1 cm of an active lesion.²⁵ Additionally, if your patient has oral disease, the recommendation is to obtain the biopsy from nonlesional buccal mucosa, especially if there is desquamative gingivitis.^26,27

The ideal biopsy size is 4 or 5 mm. If considering both DIF and histopathology, it is best to procure 2 separate specimens. One larger biopsy can be carefully bisected in 2 but often is subject to more handling artifacts, which can affect findings. In the case of 1 biopsy bisected into 2 specimens, the punch should be at least 6 mm. Shave biopsies also can be performed as long as they extend into the reticular dermis.²³

For vasculitis, biopsies for DIF should be taken from lesions that are less than 24 hours old for highest yield, as the level of tissue immunoreactants tends to decline over time.²⁸ This guideline does differ from hematoxylin and eosin specimens sent for evaluation of vasculitis, which ideally should be lesional tissue over 72 hours old. When evaluating for lupus (including subacute cutaneous lupus, discoid lupus, and systemic lupus), DIF is more likely to be positive in well-established, active lesions.

Which Test Should I Order?

The answer to this question depends, but the use of all 3 tests has a specificity close to 100% when evaluating for autoantibody-associated diseases.²³ For autoimmune blistering disease, DIF is considered the diagnostic standard. The sensitivity of DIF for diagnosing BP is in the range of 82% to 90.5%, while specificity is 98%.^29-31 Other autoimmune blistering diseases, such as pemphigus or dermatitis herpetiformis, have even higher sensitivities and specificities. Direct immunofluorescence often is used as a screening test, but false negatives do occur.^32,33 Although rare, false positives also can occur, especially in cases of infection, and should be suspected when there is a lack of clinicopathologic correlation.³⁴ If DIF is negative but clinical suspicion remains high, IIF should be ordered to directly evaluate a patient’s serum for autoantibodies.

In acute cutaneous lupus, subacute cutaneous lupus, and discoid lupus, DIF of active lesions may be helpful if histopathologic examination of a cutaneous lupus erythematosus lesion is nondiagnostic. However, histopathologic examination of formalin-fixed tissue remains the standard for these diagnoses. In vasculitis, while DIF is not used for diagnosis, it is useful to evaluate for IgA deposition. This is important in adults, as IgA deposition has been associated with a greater risk for developing end-stage renal disease.³⁵

Final Thoughts

This is an overview of the tests available for diagnosing autoimmune blistering diseases. Residents should keep in mind that these tests are just one part of the puzzle when it comes to diagnosing these diseases. Results of DIF, IIF, and ELISA testing should be considered in conjunction with patient history and physical examination as well as histopathologic examination of lesional tissue when evaluating for dermatologic diseases with autoantibodies.

Direct immunofluorescence (DIF) is the go-to diagnostic test when evaluating vesiculobullous eruptions, connective tissue disease, and vasculitis. This specialized test allows visualization of autoantibodies and their reaction products in the epidermis and dermis (skin) and epithelium and subepithelium (mucosa). Indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) are additional tests that can help in the diagnosis of autoimmune blistering disease. In the blistering autoimmune diseases, the autoantibodies target components in skin and mucous membranes that are essential for cell-cell and cell-matrix adhesion causing separation within or beneath the epidermis, depending on where the target components are located. This article is intended to serve as a helpful primer for immunofluorescence testing in dermatology, with an overview of the tests available as well as pragmatic tips for optimal biopsy sites and specimen transport.

Direct Immunofluorescence

Immunofluorescence techniques date back to 1941 when Albert Coons, an American physician, pathologist, and immunologist, fluorescently labelled antibodies to visualize pneumococcal antigens in infected tissues.^1-3 In dermatology, similar methodology was used to visualize the deposition of immunoglobulins and complement in the skin of patients with systemic lupus erythematosus in 1963.⁴ Basement membrane zone antibodies were first visualized via DIF in bullous pemphigoid in 1967.⁵ This elegant test utilizes specific antibodies labeled with fluorophores that are then incubated with the patient’s tissue, ultimately forming antibody-antigen conjugates that can be visualized with a fluorescent microscope. Antibodies usually include IgG, IgM, IgA, fibrinogen, and C3. Some institutions also evaluate for IgG4.

Transport medium is critical for proper evaluation of tissues using DIF. Inappropriate storage of tissue can degrade the antigen and confuse the interpretation of specimens. An acceptable medium for DIF includes Michel transport medium, which allows tissue to be stored for days while being transported at ambient temperature without loss of signal.^6,7 Zeus medium also can be used and is more readily available. Alternatively, biopsy tissue can be snap frozen using liquid nitrogen. Specimens also may be stored on saline gauze but should be analyzed within 24 to 48 hours.⁸ Most importantly, do not place the specimen in formalin; even a brief soak in formalin can greatly alter results, especially when trying to diagnose pemphigus.⁹ Proper transport conditions are critical to prevent autolysis, mitigate putrefaction, and preserve morphology while maintaining antigenicity.¹⁰

Indirect Immunofluorescence

Indirect immunofluorescence can be helpful for detecting antibodies circulating in patient serum. Indirect immunofluorescence can be used to help diagnose pemphigoid, pemphigus, epidermolysis bullosa acquisita, bullous lupus erythematosus, and dermatitis herpetiformis. Serum testing also can be a helpful alternative when obtaining tissue is difficult, such as in children.

Indirect immunofluorescence is a 2-part technique that takes a bit longer to assay than DIF.¹¹ The first step involves incubating prepared tissue substrates with patient serum. Unlabeled antibodies in the patient serum are allowed to bind to antigens in the substrate tissue for about 30 minutes. Doubling dilutions of patient serum can be performed to titer antibody levels. The second step uses fluorescein-labeled antihuman antibodies to recognize the antigen-antibody conjugates. Normal whole tissues (eg, monkey esophagus for pemphigus vulgaris, rat bladder for paraneoplastic pemphigus, salt-split normal human skin substrate for pemphigoid and epidermolysis bullosa) are the usual substrates for testing.^11,12 Again, this test requires serum and should be collected in a red-top tube or serum-separator tube. Usually, a minimum of 0.5 mL is required for testing, but check with your preferred immunodermatology send-out laboratory before collecting.¹³

Indirect immunofluorescence usually involves an initial screening panel using 1 or 2 tissue substrates followed by individual antigen-specific assays that correspond to the clinical suspicion and IIF screening results.¹¹ Salt-split skin is used to localize basement membrane zone autoantibodies to either the epidermal (roof) or dermal (floor) side. Although many dermatopathology laboratories offer DIF testing, IIF is more specialized and may be a send-out test at your institution.

Enzyme-linked Immunosorbent Assays

Another tool in the immunodermatology armamentarium is ELISA. Commercial ELISA systems are available for the detection of autoantibodies against bullous pemphigoid (BP) antigen 180, BP230, type VII collagen, desmoglein (Dsg) 1, Dsg3, and envoplakin.¹¹ This test allows semiquantitative measurement of antibody levels and thus can be used to monitor response to treatment or identify relapse and treatment failure.¹¹ For example, in BP, significantly increased baseline anti-BP180 IgG levels correlate with 1-year mortality rates (P=.001) and relapse rates (P=.041).^14,15 Numerous additional studies support the observation that monitoring anti-BP180 as a potential marker of disease relapse can be helpful.^16,17 In pemphigus, the presence or increase of autoantibodies at remission, either anti-Dsg3 or anti-Dsg1, may be a useful tool in predicting disease relapse.¹⁸ It is important for physicians to be aware of this to be able to offer guidance on prognosis.

Knowing where to biopsy can be confusing when beginning residency. But the short answer is, it depends. Let your clinical suspicion guide your specimen site. The Figure provides a quick reference for which location will give you the highest yield for a specific diagnosis.

A few cardinal rules should guide which site is biopsied. Avoid obtaining specimens from the lower extremities as much as possible, as this site has been linked with false-negative results, especially in bullous pemphigoid.^19,20 As a dependent area prone to stasis, this site gets a lot of abuse and inflammatory changes secondary to everyday insults that can theoretically alter DIF findings, especially fibrinogen deposition.

Although tissue sent for hematoxylin and eosin staining should be lesional, biopsy for DIF ideally should not contain a new or active blister, ulcer, erosion, or bulla. Immunoreactants are more likely to be degraded in these areas, and DIF may be falsely negative.²¹

It is worthwhile to briefly discuss the definitions of the terms perilesional and nonlesional. Perilesional skin most frequently refers to skin adjacent to a bulla or vesicle. This skin can be erythematous/inflamed or appear normal. When obtaining tissue for a diagnosis of blistering disease, the general recommendation is to obtain the biopsy from lesional nonbullous skin or perilesional uninvolved skin within 1 cm of the bulla.^22-24 The only exception to this is dermatitis herpetiformis, which is best diagnosed on tissue obtained from normal-appearing perilesional skin within 1 cm of an active lesion.²⁵ Additionally, if your patient has oral disease, the recommendation is to obtain the biopsy from nonlesional buccal mucosa, especially if there is desquamative gingivitis.^26,27

The ideal biopsy size is 4 or 5 mm. If considering both DIF and histopathology, it is best to procure 2 separate specimens. One larger biopsy can be carefully bisected in 2 but often is subject to more handling artifacts, which can affect findings. In the case of 1 biopsy bisected into 2 specimens, the punch should be at least 6 mm. Shave biopsies also can be performed as long as they extend into the reticular dermis.²³

For vasculitis, biopsies for DIF should be taken from lesions that are less than 24 hours old for highest yield, as the level of tissue immunoreactants tends to decline over time.²⁸ This guideline does differ from hematoxylin and eosin specimens sent for evaluation of vasculitis, which ideally should be lesional tissue over 72 hours old. When evaluating for lupus (including subacute cutaneous lupus, discoid lupus, and systemic lupus), DIF is more likely to be positive in well-established, active lesions.

Which Test Should I Order?

The answer to this question depends, but the use of all 3 tests has a specificity close to 100% when evaluating for autoantibody-associated diseases.²³ For autoimmune blistering disease, DIF is considered the diagnostic standard. The sensitivity of DIF for diagnosing BP is in the range of 82% to 90.5%, while specificity is 98%.^29-31 Other autoimmune blistering diseases, such as pemphigus or dermatitis herpetiformis, have even higher sensitivities and specificities. Direct immunofluorescence often is used as a screening test, but false negatives do occur.^32,33 Although rare, false positives also can occur, especially in cases of infection, and should be suspected when there is a lack of clinicopathologic correlation.³⁴ If DIF is negative but clinical suspicion remains high, IIF should be ordered to directly evaluate a patient’s serum for autoantibodies.

In acute cutaneous lupus, subacute cutaneous lupus, and discoid lupus, DIF of active lesions may be helpful if histopathologic examination of a cutaneous lupus erythematosus lesion is nondiagnostic. However, histopathologic examination of formalin-fixed tissue remains the standard for these diagnoses. In vasculitis, while DIF is not used for diagnosis, it is useful to evaluate for IgA deposition. This is important in adults, as IgA deposition has been associated with a greater risk for developing end-stage renal disease.³⁵

Final Thoughts

This is an overview of the tests available for diagnosing autoimmune blistering diseases. Residents should keep in mind that these tests are just one part of the puzzle when it comes to diagnosing these diseases. Results of DIF, IIF, and ELISA testing should be considered in conjunction with patient history and physical examination as well as histopathologic examination of lesional tissue when evaluating for dermatologic diseases with autoantibodies.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase and aspartate transaminase as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase and aspartate transaminase as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

While often linked to deleterious outcomes in certain disease states, the hepatocyte-produced inflammatory marker C-reactive protein (CRP) may be a checkpoint that protects against acetaminophen-induced acute liver injury, according to research findings.

Based on the study findings, researchers believe long-term suppression of CRP function or expression may increase an individual’s susceptibility to acetaminophen-induced liver injury. In contrast, CRP “could be exploited as a promising therapeutic approach to treat hepatotoxicity caused by drug overdose” wrote study authors Hai-Yun Li, MD, of the Xi’an Jiaotong University in Shaanxi, China, and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

According to Dr. Li and colleagues, a major cause of acute liver failure is acetaminophen-induced liver injury, but despite this risk, very few treatment options for this condition exist. The only approved treatment for this complication is N-acetyl cysteine (NAC).

Although CRP represents a marker for inflammation following tissue injury, a study from 2020 and one from 2018 suggest the protein regulates complement activation and may modulate responses of immune cells. The authors of the current study noted that few studies have explored what roles complement activation and modulated immune cell responses via CRP play in acetaminophen-induced acute liver injury.

To further elucidate the role of CRP in this setting, Dr. Li and researchers assessed the mechanisms of CRP action both in vitro as well as in CRP mice with Fcy receptor 2B knockout. The researchers suggested CRP may modulate immune cell responses via these receptors. Additionally, the investigators assessed CRP action in mice with C3 knockout, given previous studies suggesting C3 knockout may alleviate acetaminophen-induced liver injury in mice. The researchers also investigated hepatic expression of CRP mutants that were defective in complement interaction. Finally, the researchers sought to understand the therapeutic potential of the inflammatory marker by performing intraperitoneal administration of human CRP at 2 or 6 hours after induction of acetaminophen-induced acute liver injury in wild-type mice.

Injection of 300 mg/kg acetaminophen over 24 hours led to overt liver injury in wild-type mice, which was characterized by increased levels of circulating alanine transaminase and aspartate transaminase as well as massive necrosis of hepatocytes. The researchers noted that these manifestations were exacerbated significantly in the CRP knockout mice.

The intravenous administration of human CRP in the mice with the drug-induced liver injury rescued defects caused by mouse CRP knockout. Additionally, human CRP administration alleviated acetaminophen-induced acute liver injury in the wild-type mice. The researchers wrote that these findings demonstrate that endogenous and human CRP “are both protective,” at least in mouse models of acetaminophen-induced liver injury.

In a second experiment, the researchers examined the mechanisms involved in CRP protection in early phases of drug-induced liver injury. Based on the experiment, the researchers found that the knockout of an inhibitory Fcy receptor mediating the anti-inflammatory activities of CRP demonstrated only “marginal effects” on the protection of the protein in acetaminophen-induced liver injury. Overall, the investigators suggested that the inflammatory marker does not likely act via the cellular Fcy receptor 2B to inhibit early phases of acetaminophen-induced hepatocyte injury. Rather, the investigators explained that CRP may act via factor H, which is recruited by CRP in regulating complement activation, to inhibit overactivation of complement on injured hepatocytes. Ultimately, the researchers explained, this results in suppression of the late phase amplification of inflammation that is mediated by neutrophils’ C3a-dependent actions.

Finally, the researchers found that intraperitoneal administration of human CRP at 2.5 mg/kg in wild-type mice at 2 hours following induction of acetaminophen-induced liver injury led to “markedly reduced liver injury,” with an efficacy that was similar to that of 500 mg/kg N-acetylcysteine, the only available treatment approved for acetaminophen-induced liver injury.

The researchers noted that N-acetylcysteine is only effective during the early phases of the acetaminophen-induced liver injury and loses effectiveness at 6 hours following injury. In contrast, human CRP in this study was still highly effective at this time point. “Given that people can tolerate high levels of circulating CRP, the administration of this protein might be a promising option to treat [acetaminophen-induced liver injury] with minimal side effects,” the researchers wrote.

The study was funded by the National Natural Science Foundation of China. The researchers reported no conflicts of interest with any pharmaceutical companies.

This article was updated on Sep. 20, 2022.

In this quiz to Dermatology News, test your current knowledge of Generalized Pustular Psoriasis. Join Abby S. Van Voorhees, MD, as she shares insights on GPP and understanding the disorder. 

Learn More

PC-US-123740 December 2021

In this quiz to Dermatology News, test your current knowledge of Generalized Pustular Psoriasis. Join Abby S. Van Voorhees, MD, as she shares insights on GPP and understanding the disorder. 

Learn More

PC-US-123740 December 2021

In this quiz to Dermatology News, test your current knowledge of Generalized Pustular Psoriasis. Join Abby S. Van Voorhees, MD, as she shares insights on GPP and understanding the disorder. 

Learn More

PC-US-123740 December 2021

The COVID-19 pandemic highlighted a major gap in our institutional infrastructure in medicine – specifically, the absence of established policies and programs to support clinician wellbeing and organizational resilience.

In a 2020 report, the National Academy of Medicine advocated for “fixing the workplace,” rather than “fixing the worker,” as a more sustainable mechanism to advance physician wellbeing and foster organizational resilience. According to the report, “A resilient organization, or one that has matched job demands with job resources for its workers and that has created a culture of connection, transparency, and improvement, is better positioned to achieve organizational objectives during ordinary times and also to weather challenges during times of crisis” (Sinsky CA et al. “Organizational Evidence-Based and Promising Practices for Improving Clinician Well-Being.” National Academy of Medicine. Nov. 2, 2020.

The report highlights six domains of evidence-based practices to support organizational resilience and improve clinician well-being: organizational commitment, workforce assessment (such as measurement of physician wellbeing and burnout); leadership (including shared accountability, distributed leadership, and the emerging role of a chief wellness officer), policy (such as eliminating and/or re-envisioning policies and practices that interfere with clinicians’ ability to provide high-quality patient care), (5) efficiency (such as minimizing administrative tasks to allow clinicians to focus on patient care), and (6) support (such as providing resources and/or policies to support work-life balance, fostering a culture of connection at work). While many organizations (including both academic and community practices) already have begun to invest in this transformation, I urge you to think creatively about whether there is more your practice can do at an organizational level to support and sustain clinician wellbeing and prevent burnout.

In this month’s issue of GIHN, we highlight AGA’s new Clinical Practice Guideline on Coagulation in Cirrhosis, as well as results from a study confirming the benefits of coffee for liver health (welcome news to the caffeine-lovers among us!). We also report on a novel text-based patient-education intervention that aims to connect patients newly diagnosed with colorectal cancer to valuable resources and support.

Thank you for your dedicated readership – we look forward to continuing to bring you engaging, clinically-relevant content in 2022!

Megan A. Adams, MD, JD, MSc
Editor in Chief

The COVID-19 pandemic highlighted a major gap in our institutional infrastructure in medicine – specifically, the absence of established policies and programs to support clinician wellbeing and organizational resilience.

In a 2020 report, the National Academy of Medicine advocated for “fixing the workplace,” rather than “fixing the worker,” as a more sustainable mechanism to advance physician wellbeing and foster organizational resilience. According to the report, “A resilient organization, or one that has matched job demands with job resources for its workers and that has created a culture of connection, transparency, and improvement, is better positioned to achieve organizational objectives during ordinary times and also to weather challenges during times of crisis” (Sinsky CA et al. “Organizational Evidence-Based and Promising Practices for Improving Clinician Well-Being.” National Academy of Medicine. Nov. 2, 2020.

The report highlights six domains of evidence-based practices to support organizational resilience and improve clinician well-being: organizational commitment, workforce assessment (such as measurement of physician wellbeing and burnout); leadership (including shared accountability, distributed leadership, and the emerging role of a chief wellness officer), policy (such as eliminating and/or re-envisioning policies and practices that interfere with clinicians’ ability to provide high-quality patient care), (5) efficiency (such as minimizing administrative tasks to allow clinicians to focus on patient care), and (6) support (such as providing resources and/or policies to support work-life balance, fostering a culture of connection at work). While many organizations (including both academic and community practices) already have begun to invest in this transformation, I urge you to think creatively about whether there is more your practice can do at an organizational level to support and sustain clinician wellbeing and prevent burnout.

In this month’s issue of GIHN, we highlight AGA’s new Clinical Practice Guideline on Coagulation in Cirrhosis, as well as results from a study confirming the benefits of coffee for liver health (welcome news to the caffeine-lovers among us!). We also report on a novel text-based patient-education intervention that aims to connect patients newly diagnosed with colorectal cancer to valuable resources and support.

Thank you for your dedicated readership – we look forward to continuing to bring you engaging, clinically-relevant content in 2022!

Megan A. Adams, MD, JD, MSc
Editor in Chief

The COVID-19 pandemic highlighted a major gap in our institutional infrastructure in medicine – specifically, the absence of established policies and programs to support clinician wellbeing and organizational resilience.

In a 2020 report, the National Academy of Medicine advocated for “fixing the workplace,” rather than “fixing the worker,” as a more sustainable mechanism to advance physician wellbeing and foster organizational resilience. According to the report, “A resilient organization, or one that has matched job demands with job resources for its workers and that has created a culture of connection, transparency, and improvement, is better positioned to achieve organizational objectives during ordinary times and also to weather challenges during times of crisis” (Sinsky CA et al. “Organizational Evidence-Based and Promising Practices for Improving Clinician Well-Being.” National Academy of Medicine. Nov. 2, 2020.

The report highlights six domains of evidence-based practices to support organizational resilience and improve clinician well-being: organizational commitment, workforce assessment (such as measurement of physician wellbeing and burnout); leadership (including shared accountability, distributed leadership, and the emerging role of a chief wellness officer), policy (such as eliminating and/or re-envisioning policies and practices that interfere with clinicians’ ability to provide high-quality patient care), (5) efficiency (such as minimizing administrative tasks to allow clinicians to focus on patient care), and (6) support (such as providing resources and/or policies to support work-life balance, fostering a culture of connection at work). While many organizations (including both academic and community practices) already have begun to invest in this transformation, I urge you to think creatively about whether there is more your practice can do at an organizational level to support and sustain clinician wellbeing and prevent burnout.

In this month’s issue of GIHN, we highlight AGA’s new Clinical Practice Guideline on Coagulation in Cirrhosis, as well as results from a study confirming the benefits of coffee for liver health (welcome news to the caffeine-lovers among us!). We also report on a novel text-based patient-education intervention that aims to connect patients newly diagnosed with colorectal cancer to valuable resources and support.

Thank you for your dedicated readership – we look forward to continuing to bring you engaging, clinically-relevant content in 2022!

Megan A. Adams, MD, JD, MSc
Editor in Chief

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Robert Herman, MD, wrote in “Rectal lesion”:

A 42-year-old healthy female was seen by me for symptoms of non-ulcer dyspepsia that was unresponsive to H2 Blockers and for assessment for screening colonoscopy. Her father had developed colon cancer at the age of 50. She denied changes in bowel habits, pattern, rectal bleeding, or melena. An EGD revealed a medium sized hiatal hernia and LA Grade B esophagitis that responded well to an OTC PPI qd.

A colonoscopy was performed and revealed a 4-cm anterior rectal “bulge” just above the hemorrhoidal plexus, appearing somewhat firm and mobile on probing the lesion with a closed biopsy forceps, and a 1 cm sessile IC valve adenomatous polyp.

And then the endoscopic medical assistant made a comment that changed everything. Read the full case discussion: https://community.gastro.org/posts/25568.
 

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Robert Herman, MD, wrote in “Rectal lesion”:

A 42-year-old healthy female was seen by me for symptoms of non-ulcer dyspepsia that was unresponsive to H2 Blockers and for assessment for screening colonoscopy. Her father had developed colon cancer at the age of 50. She denied changes in bowel habits, pattern, rectal bleeding, or melena. An EGD revealed a medium sized hiatal hernia and LA Grade B esophagitis that responded well to an OTC PPI qd.

A colonoscopy was performed and revealed a 4-cm anterior rectal “bulge” just above the hemorrhoidal plexus, appearing somewhat firm and mobile on probing the lesion with a closed biopsy forceps, and a 1 cm sessile IC valve adenomatous polyp.

And then the endoscopic medical assistant made a comment that changed everything. Read the full case discussion: https://community.gastro.org/posts/25568.
 

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Robert Herman, MD, wrote in “Rectal lesion”:

A 42-year-old healthy female was seen by me for symptoms of non-ulcer dyspepsia that was unresponsive to H2 Blockers and for assessment for screening colonoscopy. Her father had developed colon cancer at the age of 50. She denied changes in bowel habits, pattern, rectal bleeding, or melena. An EGD revealed a medium sized hiatal hernia and LA Grade B esophagitis that responded well to an OTC PPI qd.

A colonoscopy was performed and revealed a 4-cm anterior rectal “bulge” just above the hemorrhoidal plexus, appearing somewhat firm and mobile on probing the lesion with a closed biopsy forceps, and a 1 cm sessile IC valve adenomatous polyp.

And then the endoscopic medical assistant made a comment that changed everything. Read the full case discussion: https://community.gastro.org/posts/25568.
 

Key clinical point: Vitamin D status was inversely associated with severe sarcopenia, impaired physical performance, and decreased skeletal muscle mass in females with rheumatoid arthritis (RA), highlighting the need to investigate vitamin D supplementation as a therapeutic strategy for sarcopenic patients with RA.

Major finding: Low 25-hydroxyvitamin D (25[OH])D status (16.0 ng/mL or lower) was significantly associated with a high prevalence of severe sarcopenia (adjusted odds ratio [aOR], 6.00; P = .0006) in females with RA. Low physical performance (aOR, 2.65; P = .0043) and skeletal muscle mass (aOR, 2.54; P = .027) were the major components of sarcopenia linked with a low serum 25(OH)D level.

Study details: This was a cross-sectional study involving 156 female outpatients with RA.

Disclosures: This study was funded by AMED and Daiichi Sankyo Co. Ltd. Several authors reported receiving research grants and speaker’s fees from various sources including Daiichi Sankyo. Some of the authors including the lead author declared no conflict of interests.

Source: Minamino H et al. Sci Rep. 2021 Oct 14. doi: 10.1038/s41598-021-99894-6.

Key clinical point: Vitamin D status was inversely associated with severe sarcopenia, impaired physical performance, and decreased skeletal muscle mass in females with rheumatoid arthritis (RA), highlighting the need to investigate vitamin D supplementation as a therapeutic strategy for sarcopenic patients with RA.

Major finding: Low 25-hydroxyvitamin D (25[OH])D status (16.0 ng/mL or lower) was significantly associated with a high prevalence of severe sarcopenia (adjusted odds ratio [aOR], 6.00; P = .0006) in females with RA. Low physical performance (aOR, 2.65; P = .0043) and skeletal muscle mass (aOR, 2.54; P = .027) were the major components of sarcopenia linked with a low serum 25(OH)D level.

Study details: This was a cross-sectional study involving 156 female outpatients with RA.

Disclosures: This study was funded by AMED and Daiichi Sankyo Co. Ltd. Several authors reported receiving research grants and speaker’s fees from various sources including Daiichi Sankyo. Some of the authors including the lead author declared no conflict of interests.

Source: Minamino H et al. Sci Rep. 2021 Oct 14. doi: 10.1038/s41598-021-99894-6.

Key clinical point: Vitamin D status was inversely associated with severe sarcopenia, impaired physical performance, and decreased skeletal muscle mass in females with rheumatoid arthritis (RA), highlighting the need to investigate vitamin D supplementation as a therapeutic strategy for sarcopenic patients with RA.

Major finding: Low 25-hydroxyvitamin D (25[OH])D status (16.0 ng/mL or lower) was significantly associated with a high prevalence of severe sarcopenia (adjusted odds ratio [aOR], 6.00; P = .0006) in females with RA. Low physical performance (aOR, 2.65; P = .0043) and skeletal muscle mass (aOR, 2.54; P = .027) were the major components of sarcopenia linked with a low serum 25(OH)D level.

Study details: This was a cross-sectional study involving 156 female outpatients with RA.

Disclosures: This study was funded by AMED and Daiichi Sankyo Co. Ltd. Several authors reported receiving research grants and speaker’s fees from various sources including Daiichi Sankyo. Some of the authors including the lead author declared no conflict of interests.

Source: Minamino H et al. Sci Rep. 2021 Oct 14. doi: 10.1038/s41598-021-99894-6.

Key clinical point: The anti-inflammatory diet did not enhance health-related quality of life in patients with rheumatoid arthritis (RA) compared with a control diet. However, physical functioning improved significantly, particularly in patients who did not alter antirheumatic medication.

Major finding: The Health Assessment Questionnaire was not significantly different between the intervention and control diet periods (P = .503); however, the physical functioning improved significantly during intervention diet vs. control diet period (mean, 5.791; 95% CI, 1.576-10.005), particularly in patients without pharmacological treatment changes (mean, 7.898; P = .036).

Study details: Findings are from the ADIRA trial, a controlled crossover trial including 50 patients with RA who were randomly assigned to either an intervention diet including foods with suggested anti-inflammatory properties and promising effects on RA symptoms (n=24) or control diet (usual Swedish diet; n=26) for 10 weeks before switching to the other diet.

Disclosures: This study received grants from the Swedish government, Swedish Research Council for Health, Working Life and Welfare, and others. No conflict of interests was reported.

Source: Turesson Wadell A et al. PLoS One. 2021 Oct 14. doi: 10.1371/journal.pone.0258716.

Key clinical point: The anti-inflammatory diet did not enhance health-related quality of life in patients with rheumatoid arthritis (RA) compared with a control diet. However, physical functioning improved significantly, particularly in patients who did not alter antirheumatic medication.

Major finding: The Health Assessment Questionnaire was not significantly different between the intervention and control diet periods (P = .503); however, the physical functioning improved significantly during intervention diet vs. control diet period (mean, 5.791; 95% CI, 1.576-10.005), particularly in patients without pharmacological treatment changes (mean, 7.898; P = .036).

Study details: Findings are from the ADIRA trial, a controlled crossover trial including 50 patients with RA who were randomly assigned to either an intervention diet including foods with suggested anti-inflammatory properties and promising effects on RA symptoms (n=24) or control diet (usual Swedish diet; n=26) for 10 weeks before switching to the other diet.

Disclosures: This study received grants from the Swedish government, Swedish Research Council for Health, Working Life and Welfare, and others. No conflict of interests was reported.

Source: Turesson Wadell A et al. PLoS One. 2021 Oct 14. doi: 10.1371/journal.pone.0258716.

Key clinical point: The anti-inflammatory diet did not enhance health-related quality of life in patients with rheumatoid arthritis (RA) compared with a control diet. However, physical functioning improved significantly, particularly in patients who did not alter antirheumatic medication.

Major finding: The Health Assessment Questionnaire was not significantly different between the intervention and control diet periods (P = .503); however, the physical functioning improved significantly during intervention diet vs. control diet period (mean, 5.791; 95% CI, 1.576-10.005), particularly in patients without pharmacological treatment changes (mean, 7.898; P = .036).

Study details: Findings are from the ADIRA trial, a controlled crossover trial including 50 patients with RA who were randomly assigned to either an intervention diet including foods with suggested anti-inflammatory properties and promising effects on RA symptoms (n=24) or control diet (usual Swedish diet; n=26) for 10 weeks before switching to the other diet.

Disclosures: This study received grants from the Swedish government, Swedish Research Council for Health, Working Life and Welfare, and others. No conflict of interests was reported.

Source: Turesson Wadell A et al. PLoS One. 2021 Oct 14. doi: 10.1371/journal.pone.0258716.

Key clinical point: Sinusitis, pharyngitis, and acute respiratory burden all raised the likelihood of developing rheumatoid arthritis (RA).

Major finding: Acute sinusitis (odds ratio [OR], 1.61; 95% CI, 1.05-2.45), chronic sinusitis (OR, 2.16; 95% CI, 1.39-3.35), asthma (OR, 1.39; 95% CI, 1.03-1.87), and burden of acute respiratory tract disease during the preindex exposure period (OR, 1.30 per 10 codes; 95% CI, 1.08-1.55) were associated with an elevated risk for RA. Acute pharyngitis was associated with seronegative RA (OR, 1.68; 95% CI, 1.02-2.74), whereas chronic rhinitis/pharyngitis was associated with seropositive RA (OR, 2.46; 95% CI, 1.01-5.99).

Study details: This was a case-control study involving 741 patients with RA matched with 2,223 healthy controls.

Disclosures: The National Institute of Arthritis and Musculoskeletal and Skin Diseases and Rheumatology Research Foundation funded this research. No conflict of interests was reported.

Source: Kronzer VL et al. J Rheumatol. 2021 Oct 15. doi: 10.3899/jrheum.210580.

Key clinical point: Sinusitis, pharyngitis, and acute respiratory burden all raised the likelihood of developing rheumatoid arthritis (RA).

Major finding: Acute sinusitis (odds ratio [OR], 1.61; 95% CI, 1.05-2.45), chronic sinusitis (OR, 2.16; 95% CI, 1.39-3.35), asthma (OR, 1.39; 95% CI, 1.03-1.87), and burden of acute respiratory tract disease during the preindex exposure period (OR, 1.30 per 10 codes; 95% CI, 1.08-1.55) were associated with an elevated risk for RA. Acute pharyngitis was associated with seronegative RA (OR, 1.68; 95% CI, 1.02-2.74), whereas chronic rhinitis/pharyngitis was associated with seropositive RA (OR, 2.46; 95% CI, 1.01-5.99).

Study details: This was a case-control study involving 741 patients with RA matched with 2,223 healthy controls.

Disclosures: The National Institute of Arthritis and Musculoskeletal and Skin Diseases and Rheumatology Research Foundation funded this research. No conflict of interests was reported.

Source: Kronzer VL et al. J Rheumatol. 2021 Oct 15. doi: 10.3899/jrheum.210580.

Key clinical point: Sinusitis, pharyngitis, and acute respiratory burden all raised the likelihood of developing rheumatoid arthritis (RA).

Major finding: Acute sinusitis (odds ratio [OR], 1.61; 95% CI, 1.05-2.45), chronic sinusitis (OR, 2.16; 95% CI, 1.39-3.35), asthma (OR, 1.39; 95% CI, 1.03-1.87), and burden of acute respiratory tract disease during the preindex exposure period (OR, 1.30 per 10 codes; 95% CI, 1.08-1.55) were associated with an elevated risk for RA. Acute pharyngitis was associated with seronegative RA (OR, 1.68; 95% CI, 1.02-2.74), whereas chronic rhinitis/pharyngitis was associated with seropositive RA (OR, 2.46; 95% CI, 1.01-5.99).

Study details: This was a case-control study involving 741 patients with RA matched with 2,223 healthy controls.

Disclosures: The National Institute of Arthritis and Musculoskeletal and Skin Diseases and Rheumatology Research Foundation funded this research. No conflict of interests was reported.

Source: Kronzer VL et al. J Rheumatol. 2021 Oct 15. doi: 10.3899/jrheum.210580.

Key clinical point: Filgotinib 200 mg (FIL200) and 100 mg (FIL100) showed similar safety/tolerability in patients with moderate-to-severe rheumatoid arthritis (RA) with over a median of 1.6 years and maximum of 5.6 years of exposure, with FIL200 showing a lower infection rate in the long term.

Major finding: Treatment-emergent adverse events (TEAEs) were similar between FIL200 (exposure-adjusted incidence rate [EAIR], 195.4 per 100 patient-years of exposure [100 PYE]), FIL100 (176.3 per 100 PYE), and placebo (175.9 per 100 PYE) during the 12-week period. During long-term exposure, EAIR for grade ≥3 TEAEs were 6.4 and 7.6 per 100 PYE for FIL200 and FIL100, respectively, but serious infectious AEs were lower with FIL200 vs. FIL100 (EAIR, 1.6 vs. 3.1 per 100 PYE).

Study details: Data come from integrated analysis of 7 clinical trials including patients with moderate-to-severe RA who received ≥1 dose of FIL200, FIL100, or placebo.

Disclosures: This study was funded by Gilead Sciences, Inc. Some investigators including the lead author reported receiving grants, honoraria, consultancy/speaker’s fees, and being an employee of or shareholder of various sources including Gilead Sciences.

Source: Winthrop KL et al. Ann Rheum Dis. 2021 Nov 5. doi: 10.1136/annrheumdis-2021-221051.

Key clinical point: Filgotinib 200 mg (FIL200) and 100 mg (FIL100) showed similar safety/tolerability in patients with moderate-to-severe rheumatoid arthritis (RA) with over a median of 1.6 years and maximum of 5.6 years of exposure, with FIL200 showing a lower infection rate in the long term.

Major finding: Treatment-emergent adverse events (TEAEs) were similar between FIL200 (exposure-adjusted incidence rate [EAIR], 195.4 per 100 patient-years of exposure [100 PYE]), FIL100 (176.3 per 100 PYE), and placebo (175.9 per 100 PYE) during the 12-week period. During long-term exposure, EAIR for grade ≥3 TEAEs were 6.4 and 7.6 per 100 PYE for FIL200 and FIL100, respectively, but serious infectious AEs were lower with FIL200 vs. FIL100 (EAIR, 1.6 vs. 3.1 per 100 PYE).

Study details: Data come from integrated analysis of 7 clinical trials including patients with moderate-to-severe RA who received ≥1 dose of FIL200, FIL100, or placebo.

Disclosures: This study was funded by Gilead Sciences, Inc. Some investigators including the lead author reported receiving grants, honoraria, consultancy/speaker’s fees, and being an employee of or shareholder of various sources including Gilead Sciences.

Source: Winthrop KL et al. Ann Rheum Dis. 2021 Nov 5. doi: 10.1136/annrheumdis-2021-221051.

Key clinical point: Filgotinib 200 mg (FIL200) and 100 mg (FIL100) showed similar safety/tolerability in patients with moderate-to-severe rheumatoid arthritis (RA) with over a median of 1.6 years and maximum of 5.6 years of exposure, with FIL200 showing a lower infection rate in the long term.

Major finding: Treatment-emergent adverse events (TEAEs) were similar between FIL200 (exposure-adjusted incidence rate [EAIR], 195.4 per 100 patient-years of exposure [100 PYE]), FIL100 (176.3 per 100 PYE), and placebo (175.9 per 100 PYE) during the 12-week period. During long-term exposure, EAIR for grade ≥3 TEAEs were 6.4 and 7.6 per 100 PYE for FIL200 and FIL100, respectively, but serious infectious AEs were lower with FIL200 vs. FIL100 (EAIR, 1.6 vs. 3.1 per 100 PYE).

Study details: Data come from integrated analysis of 7 clinical trials including patients with moderate-to-severe RA who received ≥1 dose of FIL200, FIL100, or placebo.

Disclosures: This study was funded by Gilead Sciences, Inc. Some investigators including the lead author reported receiving grants, honoraria, consultancy/speaker’s fees, and being an employee of or shareholder of various sources including Gilead Sciences.

Source: Winthrop KL et al. Ann Rheum Dis. 2021 Nov 5. doi: 10.1136/annrheumdis-2021-221051.